Mesothelioma Gene Therapy Trial at Penn Medicine Open, Shows Promise
March 7, 2012
If his enthusiasm Tuesday night for the latest clinical trial at the University of Pennsylvania School of Medicine was any indication, Daniel Sterman, M.D., is in the midst of a mesothelioma breakthrough.
Gene therapy is working.
“We only started this trial a year ago. The crude data is very preliminary, but very, very impressive,” Sterman said. “Our goal . . . is to turn this from a death sentence into a chronic disease that people can live with for years.”
Sterman spoke on a teleconference sponsored by the Mesothelioma Applied Research Foundation, as part of its “Meet the Experts” series.
A diagnosis of pleural mesothelioma typically has been met with a grim prognosis, six to 18 months to live. Even with major surgery and a multi-pronged approach to therapy, the outcome often doesn’t change significantly.
“We’ve been trying for 18 years now to bring gene therapy closer to mainstream therapy for mesothelioma,” he said. “Advances in medicine can move slowly. This has moved slower than anyone anticipated, but we’re excited now where we are, what we’re seeing.”
Sterman expects to be presenting soon on results showing an 80 percent response rate to treatment and tumor shrinkage — double the rate in contrast to other treatments — for his combination of gene therapy coupled with a standard chemotherapy regimen.
He talked about one mesothelioma patient, 14 years after an early version of gene therapy, now living in Australia, needing only help for an occasional bout with pleural inflammation. Her own immune system has kept the mesothelioma in check, thanks to the gene therapy.
He talked about another mesothelioma patient, elderly, sick and exhausted from previous treatments that didn’t work, living 10 more years after gene therapy caused a sudden turnaround.
With gene therapy, a patient is infected with a virus that has been genetically altered and redesigned to replace the defective copy of the same gene. If the copy functions correctly, it enters the cells and produces viral proteins that eliminate the defective ones.
If working correctly, the genetically-altered cells also trigger a body’s own immune system to continue fighting off any mesothelioma growth.
“We had one (recently) with a 75 percent reduction in the tumor,” Sterman said. “(In this trial) we can provide all the benefits of standard therapy, along with the exciting prospects of genetic therapy.”
Sterman said Tuesday that he has had 15 patients in the latest trial with three more patients already scheduled for April. His goal is to have 40 patients by the end of 2012. His ideal patient would be one who is newly diagnosed, often one who was not a candidate for surgery, or one who elected not to have surgery.
The Trial Routine
The typical start for this trial is with an initial blood test to determine if the patient qualifies as a candidate, and to measure the level of antibodies against the virus.
A week later, a catheter is inserted. A week after the catheter, a patient is admitted on Monday and given the first dose of gene therapy, then monitored for 24 hours. On Thursday, a second dose is provided. On Friday, the catheter can be removed.
Ten days later, the patient begins the first of six rounds of chemotherapy. Only the first three rounds must be done at Penn Medicine so that the overlap of side effects can be monitored.
The trial also is cost effective. While most insurance plans cover the chemotherapy, the gene therapy is covered by a National Cancer Institute grant. A patient’s biggest cost is travel and lodging.
Anyone interested in the trial can call the Abramson Cancer Center at 800-789-PENN.
Gene therapy and mesothelioma is a relatively new combination. The research originally was aimed at fighting cystic fibrosis. Twenty years ago, scientists believed that gene therapy was such a breakthrough that eventually it could replace treatments for most cancers, and become a cure. The progress, though, has been slow.
“Our goal now is to be able to deliver a treatment to patients that would stay for their lifetimes, enabling a patient’s own cells to control the tumors,” he said. “We truly believe this combination will work far better (than anything else). We can deliver the treatment into a space the size of quarter, and get a response from all parts of the body.”